This invention relates to the treatment of neurological disorders, and more particularly techniques for the treatment of epileptic seizures.
Epilepsy is a condition characterized by recurrent seizures, which are the outward manifestation of excessive and/or hyper-synchronous abnormal electrical activity of neuronal structures of the brain. A seizure occurs when the electrical activity of brain structures or even the whole brain becomes abnormally xe2x80x9csynchronized.xe2x80x9d This is the operational definition of an epileptic seizure.
A seizure patient may suffer from any combination of different types of seizures. Grand mal seizures are the most common form of epilepsy and are characterized by convulsions with tonic-clonic contractions of the muscles. Absence seizures (previously referred to as xe2x80x9cpetit malxe2x80x9d) are characterized by a brief and sudden loss of consciousness. The psychomotor form of seizures is characterized by a clouding of consciousness for one or two minutes. A complex partial seizure is characterized by a complete loss of consciousness. The type of seizure experienced is typically dependent upon the portion of the cerebral cortex where hypersynchronous activity is occurring. Many types of seizures generally involve the entire brain, while certain types, such as partial seizures, begin in one part of the brain and may remain local.
Regardless of the type of epilepsy, seizures significantly limit the autonomy of the patient. When hit with a seizure, the patient typically loses some level of control of his/her body. In most cases, seizures occur without prior warning to the patient. As a result, epileptic seizures pose a serious safety hazard to the patient and others surrounding the patient. For example, a patient hit with a sudden seizure while driving a car may endanger the patient""s own safety as well as the safety of others. Seizure patients are also exposed to a risk of bodily harm when operating machinery and even in daily activities such as crossing a street or going down stairs. In addition to this safety hazard, each seizure will further damage brain structures often resulting in progressive loss of brain function over time.
Researchers have developed a number of techniques for treating seizure disorders and its symptoms. For example, research has shown that inhibiting (namely, reducing the excitation of neurons) the substantia nigra in the brain increases the threshold for seizure occurrence. Researchers have also found that increasing the activity of neurons in the external Globus Pallidum (GPe) increases inhibition of neurons in the subthalamic nucleus, which in turn inhibits neural activity in the substantia nigra.
Neurosurgeons have also been able to diminish the symptoms of many neural disorders by lesioning certain brain areas. Examples include lesioning the ventral lateral portion of the internal Globus Pallidus and the Vim Thalamus for treating movement disorders. Electrical stimulation of the nervous system has also been used to suppress seizures. Finally, infusion of certain drugs into a region of the brain can affect the excitability of the neurons at the site of infusion as disclosed in U.S. Pat. No. 5,713,923 (Ward et al.) assigned to Medtronic, Inc.
Others have studied the effects of electrically stimulating the vagus nerve as a means of suppressing epileptic activity. It has been observed that stimulation of the vagus nerve with certain parameters caused de-synchronization of the brain""s electrical activity in animal models. These concepts were disclosed by Zabara in U.S. Pat. Nos. 4,867,164 and 5,025,807.
Under another approach, researchers have devised algorithms to detect the onset of a seizure. Qu and Gotman reported a system that recognizes patterns of electrical activity similar to a template developed from recording an actual seizure. See H. Qu and J. Gotman, xe2x80x9cA Seizure Warning System for Long-term Epilepsy Monitoringxe2x80x9d, Neurology, 1995;45:2250-2254. Also, see I. Osario, M. Frei, D. Lerner, S. Wilkinson, xe2x80x9cA Method for Accurate Automated Real-time Seizure Detectionxe2x80x9d, Epilepsia, Vol. 36, Suppl. 4, 1995. In each of these techniques for recognizing the onset of a seizure, the developers employ two processes. The first process is to extract certain features from the signals representing the electrical activity of the brain. Examples of the signal features include the signal power or the frequency spectrum of the signals. The second process is to recognize a pattern or set of values for those features that characterize a brain state that will reliably lead to a seizure.
Using pattern recognition techniques, closed-looped protocols for responding to the onset of an epileptic seizure have also been suggested. For example, U.S. Pat. Nos. 6,128,538 and 6,134,474 report closed-loop systems for identifying and responding to a neurological disease, such as epilepsy. These systems, however, identify and respond to neurological events that have already begun. Once started, these events may be difficult to correct. Therefore, a need for more efficient and effective treatments of neurological events continues to exist. Table 1 lists documents that disclose systems and methods that provide for seizure detection.
All documents listed in Table 1 above are hereby incorporated by reference herein in their respective entireties. As those of ordinary skill in the art will appreciate readily upon reading the Summary of the Invention, Detailed Description of the Preferred Embodiments and claims set forth below, many of the devices and methods disclosed in the patents of Table 1 may be modified advantageously by using the techniques of the present invention.
The present invention has certain objects. That is, various embodiments of the present invention provide solutions to one or more problems existing in the prior art with respect to the treatment of neurological disorders, and with respect to the treatment of epileptic seizures in particular. Such problems include, for example, treating neurological events only after they have started and, in particular, treating epileptic seizures only after they have started, the present inability to predict the likelihood of the occurrence of an impending neurological event, the present inability to predict the likelihood of the occurrence of an impending epileptic seizure, the present inability to provide therapy to a patient in order to avert the onset of an impending, but not yet started, neurological event, and the present inability to provide therapy to a patient in order to avert the onset of an imminent, but not yet started, epileptic seizure. Various embodiments of the present invention have the object of solving at least one of the foregoing problems.
It is an object of the present invention to overcome at least some of the disadvantages of the foregoing systems by providing a system and method that probe the excitable state of the brain or a specific sub region of the brain and relate a measurement acquired via the probe to the likelihood of the occurrence of an impending neurological event.
It is a further object of the invention to provide a method of signal analysis to predict the likelihood of the occurrence of a neurological disorder or event prior to the start of the event and to provide therapy to the brain when a neurological disorder and/or event is predicted.
In addition, it is an object of the invention to provide an implantable system for delivering electrical stimuli to and analyzing response field potentials from the brain to predict the likelihood of the occurrence of a neurological disorder and/or event prior to the start of the event.
It is another object of the invention to provide a system and method of signal analysis to predict the likelihood of the occurrence of an impending epileptic seizure.
It is an object of the invention to determine a level of functional interconnectivity in brain structures and to use the level in the prediction of impending neurological disorders.
Various embodiments of the invention may possess one or more features capable of fulfilling the above objects. Instead of sensing and responding to a neurological event that has already begun, the present invention involves sensing and responding to precursors of an impending neurological event. Therapy can then be delivered to avert the onset of the neurological event. Therapy to prevent an impending neurological event may be less traumatic for the patient and less demanding on system resources, e.g., battery energy levels, for treating the event.
Some embodiments of the invention include one or more of the following features: one or more electrodes implantable in a structure of a brain and a signal processor/generator coupled to the electrodes; the signal generator including an electrical pulse generator to deliver electrical stimuli to the brain via the electrodes implanted in the structure of the brain; the signal generator including a signal analyzer to receive via the electrodes response field potentials to the electrical stimuli delivered with the electrical pulse generator; the signal analyzer receiving response field potentials through the electrodes and predicting the likelihood of the occurrence of a neurological disorder based on the sensed response field potentials.
The invention involves predicting the likelihood of occurrence of neurological disorders within the brain by chronically measuring and analyzing the excitable state of the brain in terms of a balance between the levels of excitation and levels of inhibition in certain parts of the brain evoked by electrical stimuli given to brain structures. The structures instrumental in this balance may or may not be the brain structures that are directly involved with the onset of the neurological disorder within the brain. Nevertheless, the balance between excitation and inhibition is used as an indicator of the likelihood that a neurological disorder, such as a seizure, is about to occur.
In one embodiment, the present invention provides for electrical stimuli to be delivered to a structure of the brain. Response field potentials to the stimuli are sensed and analyzed to predict the occurrence of a neurological disorder. In an alternative embodiment, response magnetic fields, and their respective vectors, are measured and analyzed to predict the occurrence of the neurological disorder. An example of such a disorder is an epileptic seizure.
Short electrical stimuli are delivered to the brain region under investigation. These stimuli will activate the nerve fibers that naturally activate the brain structures. Activity of the nerve cells is accompanied by an electrical field in their immediate surrounding, the local field potential, which can be measured with indwelling electrodes and under the right circumstances used to deduce the cellular activity. Alternatively, the activity of the nerve cell is accompanied by a magnetic field in their immediate surrounding, the local magnetic field potential and associated vectors, are used to deduce the cellular activity. In the present invention, single electrical stimuli can be used. However, more complex spatially and temporally organized sets of stimuli can be used in order to test the excitable state of the local neuronal circuit.
Using combinations of well timed stimuli will bring the structure in highly specific states of excitability and allow to extract among other aspects the balance between excitation and inhibition. The typical and most simple example is to give two successive stimuli, the first one puts the region into an excitable state (which can be measured) such that the second can then be used to measure the relative level of inhibition.
The electrical stimuli delivered to the brain can include pairs of two or more electrical stimuli. For example, such a pulse pattern can include a repetitively delivered pair of stimuli having a first stimulus and a second stimulus. The response field potentials of the brain to the first and second stimuli are sensed and measurements of change in the responses made. The change in the response field potentials is used to determine a level of functional interconnectivity in structures of the brain affected by the given stimuli. In an alternative embodiment, response magnetic fields, and their respective vectors, are measured and analyzed to determine the level of functional interconnectivity in structures of the brains affected by the given stimuli.
The level of functional interconnectivity can be determined by calculating a ratio of the response field potentials, or response magnetic fields, resulting from the pairs of first and second stimuli. A plot of the ratio indicates the level of functional interconnectivity in structures of the brain influenced by the stimuli. Features from the plot of the ratio may indicate when a neurological event is imminent. For example, possible features from the plot include, but are not limited to, rising (positive) or falling (negative) slope of the response, under or overshoot, time to peak, half width of the response, description of the response with an alfa-function, or a series of exponential functions raised to any order. When these features are identified, therapy can be delivered to treat the impending neurological event. Both the sensing and therapeutic aspects of the invention can be embodied or delivered via an implantable device that is carried by the patient for continuous use.
In comparison to known implementations of detecting and treating neurological disorders, various embodiments of the present invention may provide one or more of the following advantages: probing the excitable state of the brain or a specific sub region of the brain and relating a measurement acquired via the probe to the likelihood of the occurrence of an impending neurological event; predicting the likelihood of the occurrence of an impending neurological event prior to the start of the event; providing therapy to the brain when a neurological disorder and/or event is predicted; and predicting the likelihood of the occurrence of an impending epileptic seizure.
The above summary of the present invention is not intended to describe each embodiment or every embodiment of the present invention or each and every feature of the invention. Advantages and attainments, together with a more complete understanding of the invention, will become apparent and appreciated by referring to the following detailed description and claims taken in conjunction with the accompanying drawings.